Congenital hydrocephalus is a common birth defect that is estimated to occur with a frequency of 0.5-1.8 per 1000 births (Howard, et al., J. Med. Genet., 18:252-255 [1981]). It has been estimated that about ⅔ of patients with congenital hydrocephalus have some degree of aqueductal stenosis (Duckett, S., Pediatric Neuropathology, p. 199 [1995]) which results in an excess of cerebrospinal fluid (CSF) in the ventricles of the brain. This excess fluid results in expansion and trauma to the surrounding brain tissue. Hydrocephalus has significant social and economic costs. In 1993, surgery for shunt placement cost almost $100 million per year. Congenital hydrocephalus also has adverse effects on the developing brain, which may persist as neurological deficits in children and adults, such as mental retardation, cerebral palsy, epilepsy and visual disabilities.
Many cases of hydrocephalus are caused by chromosome X-linked genetic mutations. Other causes of congenital and familial congenital hydrocephalus are unknown. Current diagnostic procedures are very limited in that they show presence of hydrocephalus after significant malformations have occurred. Some of these diagnostic procedures for hydrocephalus include x-ray, magnetic resonance imaging (MRI) and CAT scans.
Regulatory factor X (RFX) members are evolutionarily conserved transcription factors that share a highly conserved winged helix DNA-binding domain. Human RFX4 contains evolutionarily conserved regions, including a RFX-type DNA-binding domain, a dimerization domain, and other conserved regions, and is closely related to RFX1, RFX2, and RFX3 in structure. RFX4 is associated with breast cancer, and is expressed in testis.
In view of these considerations, there is a need for systems and methods for better understanding, diagnosing, and controlling the complex biological processes that result in congenital hydrocephalus.